Li Xinyi, Wang Jin, Song Xuemin, Wu Huisheng, Guo Peipei, Jin Zhao, Wang Chengyao, Tang Chaoliang, Wang Yanlin, Zhang Zongze
a Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.
b Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China; Department of Anesthesiology, The First Affiliated Hospital of USTC; Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China.
Can J Physiol Pharmacol. 2018 Sep;96(9):886-892. doi: 10.1139/cjpp-2018-0046. Epub 2018 Jul 5.
This study aimed to investigate the protective effects of ketamine against hepatic ischemia-reperfusion (I/R) injury by suppressing activation of Kupffer cells (KCs) in rat liver autotransplantation. Male Sprague-Dawley rats were randomized into 3 groups (n = 10 each). Group I, the sham group, received saline. Group II received saline and underwent orthotopic liver autotransplantation (OLAT). Group III received 10 mg/kg ketamine and underwent OLAT. Blood samples were obtained at 3, 6, 12, and 24 h after I/R, and following ALT, AST, LDH, IL-6, TNF-α, IL-1β, and IL-10 in serum were detected. Model rats were sacrificed at the indicated time points and the graft liver tissues were evaluated histologically. KCs were isolated from rat liver tissues, and inflammatory products and proteins of NF-κB signaling pathway were detected using quantitative RT-PCR and Western blotting. Our results showed that ketamine significantly decreased ALT, AST, LDH, IL-6, TNF-α, and IL-1β levels and increased IL-10 level. Furthermore, ketamine alleviated the histopathology changes, by less KC infiltration and lower hepatocyte apoptosis. Moreover, activity of NF-κB signaling pathway in KCs was suppressed. In addition, production of pro- and anti-inflammatory factors is consistent with the results in tissues. Ketamine ameliorated I/R injury after liver transplantation by suppressing activation of KCs in rats.
本研究旨在通过抑制大鼠肝脏自体移植中库普弗细胞(KCs)的激活,探讨氯胺酮对肝缺血再灌注(I/R)损伤的保护作用。将雄性Sprague-Dawley大鼠随机分为3组(每组n = 10)。第一组为假手术组,给予生理盐水。第二组给予生理盐水并进行原位肝脏自体移植(OLAT)。第三组给予10 mg/kg氯胺酮并进行OLAT。在I/R后3、6、12和24小时采集血样,检测血清中的ALT、AST、LDH、IL-6、TNF-α、IL-1β和IL-10。在指定时间点处死模型大鼠,对移植肝脏组织进行组织学评估。从大鼠肝脏组织中分离KCs,采用定量RT-PCR和蛋白质印迹法检测炎症产物和NF-κB信号通路蛋白。结果显示,氯胺酮显著降低了ALT、AST、LDH、IL-6、TNF-α和IL-1β水平,提高了IL-10水平。此外,氯胺酮减轻了组织病理学变化,减少了KC浸润,降低了肝细胞凋亡。此外,KCs中NF-κB信号通路的活性受到抑制。此外,促炎和抗炎因子的产生与组织中的结果一致。氯胺酮通过抑制大鼠KCs的激活改善了肝移植后的I/R损伤。